Thrombospondin-1 (TSP-1) promotes the invasive properties of human breast cancer.
Thrombospondin-1 (TSP-1) promotes the invasive properties of human breast cancer.
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DOI：
10.1006/jsre.1996.0219
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发表时间：
1996-06
期刊：
影响因子：
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通讯作者：
Thomas N. Wang;Xiaoli Qian;M. Granick;M. Solomon;V. Rothman;D. Berger;G. Tuszynski
中科院分区：
文献类型：
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作者：
Thomas N. Wang;Xiaoli Qian;M. Granick;M. Solomon;V. Rothman;D. Berger;G. Tuszynski
TSP-1是一种与基质结合的粘附糖蛋白，在肿瘤细胞增殖和肿瘤血管生成中发挥作用。本研究旨在探讨TSP-1对乳腺癌细胞侵袭能力的影响。使用具有胶原蛋白包被膜的改良的Boyden室装置进行肿瘤细胞侵袭测定。在无血清培养基中研究了四种乳腺细胞系：恶性MDA-MB-231、SKBR-3和MCF-7细胞系，以及良性MCF-10A细胞系。侵袭被测量为在3小时孵育期后穿过胶原屏障的五个代表性高功率场（400 x）中的细胞数量的总和。还在恶性细胞系中评价了抗TSP-1抗体（100微克/ml）的作用。通过ANOVA和学生非配对t检验进行统计分析。在所有三种恶性细胞系中，与缓冲液对照相比，TSP-1促进了侵袭的剂量依赖性增加。TSP-1（100 nM）促进MDA-MB-231、SKBR-3和MCF-7细胞系的肿瘤细胞侵袭比对照增加5倍以上（P < 0.005）。TSP-1对良性细胞MCF-10A的侵袭力没有影响。在MDA-MB-231、SKBR-3和MCF-7细胞系中，抗TSP-1抗体分别抑制TSP-1促进的侵袭45%、48%和39%（P = 0.003、0.044、0.047）。TSP-1促进乳腺癌细胞对胶原蛋白的肿瘤细胞侵袭。设计抑制TSP-1的治疗可以预防乳腺癌的侵袭和转移。
TSP-1 is a matrix-bound adhesive glycoprotein, which plays a role in tumor cell proliferation and tumor angiogenesis. The purpose of this study was to investigate the effect of TSP-1 on breast tumor cell invasion. Tumor cell invasion assays were performed using a modified Boyden chamber apparatus with collagen-coated membranes. Four breast cell lines were studied in serum-free media: the malignant MDA-MB-231, SKBR-3, and MCF-7 cell lines, and the benign MCF-10A cell line. Invasion was measured as the summation of the number of cells in five representative high power fields (400x) traversing the collagen barrier after a 3-hr incubation period. The effect of an anti-TSP-1 antibody (100 microgram/ml) was also evaluated in the malignant cell lines. Statistical analysis was performed by ANOVA and Student's unpaired t test. TSP-1 promoted a dose-dependent increase in invasion as compared to buffer controls in all three malignant cell lines. TSP-1 (100 nM) promoted a greater than five-fold increase over controls in tumor cell invasion for MDA-MB-231, SKBR-3, and MCF-7 cell lines (P < 0.005). TSP-1 had no effect on the invasiveness of the benign cell type MCF-10A. Anti-TSP-1 antibody inhibited TSP-1 promoted invasion in the MDA-MB-231, SKBR-3, and MCF-7 cell lines by 45, 48, and 39%, respectively (P = 0.003, 0.044, 0.047). TSP-1 promotes tumor cell invasion of collagen by breast cancer cells. Therapy designed to inhibit TSP-1 may prevent invasion and metastasis in breast cancer.